Increase of somatic cell mutations in oxidative damage-sensitive drosophila.

BACKGROUND

Oxidative damage is an important genotoxic source for almost all organisms. To efficiently detect mutations induced by oxidative damage, we previously developed a urate-null Drosophila strain. Using this Drosophila strain, we showed the mutagenic activity of environmental cigarette smoke (ECS) and the herbicide paraquat, which are known to produce reactive oxygen species (ROS). In the present study, we examined the mutagenic activities of carcinogenic mutagens that are considered to cause mutations by adduct formation, alkylation, or crosslinking of cellular DNA in the oxidative damage-sensitive Drosophila to evaluate how the oxidative damage induced by these mutagens is involved in causing mutations. In addition, we evaluated whether these oxidative damage-sensitive flies may be useful for mutation assays.

METHODS

We performed the wing-spot test in oxidative damage-sensitive Drosophila (urate-null strains) to examine the mutagenicity of 2-amino-3,8-dimethylimidazo[4,5-]-quinoxaline (MeIQx), mitomycin C (MMC), 4-nitroquinoline N-oxide (4NQO), -nitrosodimethyl-amine (NDMA), and -nitrosodiethylamine (NDEA). We also observed the mutagenicity of X-ray irradiation as a control in which mutations should be mainly caused by oxidative damage.

RESULTS

As expected, the mutagenic activity of X-ray irradiation was higher in the urate-null Drosophila than in the wild-type Drosophila. The mutagenic activities of the tested compounds were also higher in the urate-null Drosophila than in the wild-type Drosophila. In experiments using another urate-null strain, the mutagenicity of -nitrosodialkylamines was also higher in the urate-null flies than in the wild-type ones.

CONCLUSIONS

The tested compounds in this study were more mutagenic in urate-null Drosophila than in wild-type Drosophila. It was supposed that ROS were generated and that the ROS might be involved in mutagenesis. The present results support the notion that in addition to causing DNA lesions via adduct formation, alkylation, or DNA crosslinking, these mutagens also cause mutations via ROS-induced DNA damage. As such, urate-null Drosophila appear to be useful for detecting the mutagenic activity of various mutagens, especially those that produce reactive oxygen. If the mutation rate increases on a mutation assay using urate-null Drosophila, it might suggest that the mutagen generates ROS, and that the produced ROS is involved in causing mutations.